FACILITATED TRANSPORT OF 6-MERCAPTOPURINE AND 6-THIOGUANINE AND NON-MEDIATED PERMEATION OF 8-AZAGUANINE IN NOVIKOFF RAT HEPATOMA-CELLS AND RELATIONSHIP TO INTRACELLULAR PHOSPHORIBOSYLATION
FACILITATED TRANSPORT OF 6-MERCAPTOPURINE AND 6-THIOGUANINE AND NON-MEDIATED PERMEATION OF 8-AZAGUANINE IN NOVIKOFF RAT HEPATOMA-CELLS AND RELATIONSHIP TO INTRACELLULAR PHOSPHORIBOSYLATION
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DOI：
10.1016/0005-2736(81)90294-7
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
ZYLKA, JM
中科院分区：
文献类型：
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作者：
PLAGEMANN, PGW;MARZ, R;ZYLKA, JM
6-巯基嘌呤和6-硫代鸟嘌呤[对肿瘤细胞有毒性]强烈抑制次黄嘌呤进入缺乏次黄嘌呤/鸟嘌呤磷酸核糖基转移酶的Novikoff大鼠肝癌细胞的零反式进入; 8-氮鸟嘌呤没有显著影响。6-巯基嘌呤被次黄嘌呤载体以与其天然底物大约相同的效率转运（Km = 372 ± 0.5）。23 μ M; Vmax = 30 ±。0.7 pmol/μ l细胞H2O/s）。8-氮鸟嘌呤进入细胞没有表现出饱和性的迹象，并且不受次黄嘌呤/鸟嘌呤载体底物的显著影响。10-100 μ M的8-氮鸟嘌呤的进入速率仅为次黄嘌呤转运的约5%，并且与其脂溶性有关，其方式与对各种物质所观察到的相同，据信这些物质通过质膜的渗透是非介导的。只有非离子化形式的8-氮鸟嘌呤（pKa = 6.6）渗透细胞膜。用野生型Novikoff细胞的研究表明，渗透到细胞中是细胞外8-氮鸟嘌呤转化为细胞内aza-GTP及其掺入核酸的主要速率决定步骤。6-巯基嘌呤被迅速转运到细胞中并磷酸核糖基化;其掺入核酸的主要速率决定步骤是6-巯基嘌呤核苷5“-单磷酸的进一步转化。
6-Mercaptopurine and 6-thioguanine [toxic to tumor cells] strongly inhibited the zero-trans entry of hypoxanthine into Novikoff rat hepatoma cells which lacked hypoxanthine/guanine phosphoribosyltransferase; 8-azaguanine had no significant effect. 6-Mercaptopurine was transported by the hypoxanthine carrier with about the same efficiency as its natural substrates (Km = 372 .+-. 23 .mu.M; Vmax = 30 .+-. 0.7 pmol/.mu.l cell H2O per s). 8-Azaguanine entry into the cells showed no sign of saturability and was not significantly affected by substrates of the hypoxanthine/guanine carrier. The rate of entry of 8-azaguanine at 10-100 .mu.M amounted to only about 5% of that of hypoxanthine transport and was related to its lipid solubility in the same manner as observed for various substances whose permeation through the plasma membrane is believed to be non-mediated. Only the non-ionized form of 8-azaguanine (pKa = 6.6) permeated the cell membrane. Studies with wild type Novikoff cells showed that permeation into the cell was the main rate-determining step in the conversion of extracellular 8-azaguanine to intracellular aza-GTP and its incorporation into nucleic acids . 6-Mercaptopurine was rapidly transported into cells and phosphoribosylated; the main rate-determining step in its incorporation into nucleic acids was the further conversion of 6-mercaptopurine riboside 5''-monophosphate.